DESCRIPTION (provided by applicants): Estrogen plays a central role in the etiology of endometrial cancer. The association of exogenous estrogen use and high endogenous hormone exposure with endometrial cancer has been well characterized. The effect of soyfoods, rich source of phytoestrogens that have both weak estrogenic and anti-estrogenic effects, has only been studied in two studies and results were inconsistent. Given the dual effect of phyotoestrogens, we hypothesize that the effect of phytoestrogens on endometrimum depends on the levels of endogenous estrogens. The level and biological effect of estrogens are determined by multiple genes and thus the risk of endometrial cancer may be associated with genetic polymorphisms of genes involved in estrogen biosynthesis, metabolism, binding and signaling, and their joint effect with soyfood intake and other lifestyle factors. To evaluate the above hypotheses, we propose to conduct a population-based case-control study including 1150 incidence cases and 1150 age-matched controls in urban Shanghai. In-person interviews will be conducted to collect dietary and other exposure information. A 10-ml peripheral blood sample (or a buccal cell sample if blood sample could not be obtained) will be collected from all cases and controls. Genomic DNA will be analyzed for the genotypes of the genes involved in estrogen biosynthesis (CYPI7, CYP19, and HSD17B1), inactivation (SUTL1AI, UGT1, and COMT), binding (SHBG), and signal transduction (ER-a and ER-b). Associations of endometrial cancer with soyfood intake and polymorphisms of above-mentioned genes will be evaluated separately, jointly and in conjunction with conditions related to estrogen levels (e.g., obesity, physical activity, dietary fat intake, and menopausal status). Incidence rate and prevalence rates of traditional risk factors (e.g., estrogen replacement therapy, obesity, nulliparity) of endometrial cancer are considerable low among women in Shanghai than their counterparts in the US, and this will minimize potential confounding effects in testing new hypotheses. Consumption level of soyfood is high and hysterectomy rates are extremely low among Chinese women, providing a unique opportunity to test the hypotheses posed in the application that are difficult to be evaluated in the U.S. population.